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Biomedical subjects

M Gramatzki

Publications and source records attributed to M Gramatzki.

81 records · Page 5Linked to original sources

Activated T cells in vivo and in vitro: divergence in expression of Tac and Ia antigens in the nonblastoid small T cells of inflammation and normal T cells activated in vitro.

Elevated numbers of non-blastoid T cells expressing either the Tac or Ia antigens were found on separate cell populations in inflammatory synovial tissues and fluids of individuals with arthritis. Those synovial T cell preparations containing Tac+ cells exhibited marked proliferation upon the addition of IL 2 without concomitant mitogen stimulation; T cell eluates containing Ia+ but not Tac+ T cells did not show significantly increased levels of blastogenesis. Paired T cell preparations from blood had only minor increases in the number of Tac+ T cells and moderate increases in the number of Ia+ cells. The blood cells did not exhibit significant proliferation to IL 2. In contrast mitogen or allogeneic activation of T cells induced blastoid cells that expressed abundant per cell amount of Ia or Tac antigens. These blastoid cells resembled the small T cells of inflammation in having only very limited overlap between the population that bore Ia antigens and those with the Tac antigen; however, there was a preponderance of Tac-bearing cells.

Antigens, Surface↗

[Immunological characterization of unusual plasmacytic tumor cells in a disseminated non-Hodgkin's lymphoma].

Using monoclonal antibodies and heterosera, tumor cells from a disseminated neoplasia were characterized that could not be classified by conventional histology. The large, sometimes multinucleated tumor cells expressed Ia antigens and were positive for immunoglobulins both at the surface and intracellularly (mu, delta, kappa). This tumor was infiltrated by a large number of T cells that comprised about two thirds of the total cell number eluted from the tumor and predominantly were of the suppressor/cytotoxic phenotype. This tumor can be defined as a lymphoma of the B cell lineage with an unusual differentiation exhibiting both Ia antigens and surface immunoglobulins in addition to plasmacytoid markers.

Antineoplastic Combined Chemotherapy Protocols↗

Cryopreserved human cultured T cells as responder cells for the quantitative measurement of interleukin-2: improvement of the assay.

Large batches of human cultured T cells (CTC) were cryopreserved for later use as responder cells in a proliferation assay for measurement of interleukin (IL)-2 activity. Cryopreservation of CTC could be carried out without considerable loss in viability and cryopreserved and fresh cells showed equally good responses to IL-2. The conditions of IL-2-dependent CTC growth were analyzed, which led to a better evaluation of test results, and had important implications for the calculation of relative IL-2 activity. The repeated use of the same batch of cryopreserved CTC reduced test variability and provided an assay system that allows reliable and reproducible measurement of human IL-2 activity.

Cells, Cultured↗

Immunologic characterization of a helper T-cell lymphoma.

The lymphocytes of a patient with a T-cell non-Hodgkin's lymphoma with peripheral blood involvement and polyclonal hypergammaglobulinemia were characterized in terms of surface markers and immunologic functions. Using the fluorescence-activated cell sorter and employing various monoclonal antibodies against T-cell surface antigens, it was shown that almost all of the patient's peripheral blood lymphocytes were positive for OKT4 and 9.3, antibodies that recognize helper T-cell subset. The circulating lymphoma cells had typical characteristics for T cells; they formed spontaneous rosettes with sheep erythrocytes and stained with the pan-T-cell antibodies 9.6 and 10.2, but did not react with other anti-T-cell monoclonal reagents such as OKT3, UCHT-1, and 3A1. The cells appeared to be mature by the fact that they did not stain with OKT6, and terminal deoxynucleotidyl transferase was undetectable. Functionally, they were able to provide "help" for antibody production, and they could be stimulated to produce moderate amounts of interleukin-2, while unable to proliferate in response to mitogens. Morphologically, some of the lymphocytes showed a deeply cleaved nucleus.

Aged↗

The comparison of different rosette assay systems for the determination of T-lymphocytes in patients with solid malignant tumors.

The number of T-lymphocytes in the peripheral blood of 51 patients with different type of solid malignancies, 33 normal controls and 10 patients with rheumatoid arthritis was determined using different variations of the sheep red blood cell (SRBC) rosetting-technique (test temperature of 4 or 29 degrees C, medium substituted with or without fetal calf serum [FCS], SRBC treated or untreated with neuraminidase). No significant differences between cancer patients and normal controls were observed in the percentages of T-lymphocytes with the 4 degrees C incubation under any of the conditions tested. In absolute counts, however, a significantly decreased number of T-cells was observed in cancer patients, most likely due to the observed significant lymphopenia in this group. When the test temperature was raised to 29 degrees C, a significantly lower rosette formation was obtained in both percentages and absolute counts of peripheral T-cells in the group of cancer patients as compared to normal individuals only when both neuraminidase treated SRBC and FCS substituted medium were used. The question of whether the observed differences in the percentages and absolute counts of peripheral T-lymphocytes between cancer patients and normal controls using this rosette assay are due to a loss of a T-cell subpopulation or to an alteration in the metabolic state of T-cells in cancer patients remains open.

Adult↗

Intralymphatic interleukin-2 in combination with zidovudine for the therapy of patients with AIDS.

In a pilot study the safety and therapeutic effects of an immunostimulatory intralymphatic treatment with natural human interleukin-2 (IL-2) in combination with zidovudine were evaluated in nine patients with AIDS. Therapy with IL-2 consisted of one subcutaneous injection of 0.1 microgram/kg IL-2, followed by four intralymphatic IL-2 infusions of 0.1 microgram/kg each within a period of up to 15 days. Enlargement of lymph nodes was seen in six and a transient increase of CD4 cells in five out of nine persons in association with the IL-2 therapy. An increase of HIV p24-antigenemia was observed only in the two patients in whom zidovudine dosage had to be reduced because of side effects. Moderate clinical side effects occurred in eight of the nine patients. Four patients developed zidovudine associated anemia. Six participants showed a favourable course of disease with survival of 25 to 54 months (median 30 months) despite a previous diagnosis of manifest AIDS before IL-2 therapy. This pilot study demonstrates that a combination therapy with intralymphatic IL-2 and zidovudine can induce positive immunomodulatory effects, even in the presence of manifest AIDS. Further studies should explore the tolerability and effects of a prolonged therapy with IL-2 in combination with a more potent antiviral drug combination therapy.

Acquired Immunodeficiency Syndrome↗

Preclinical studies combining bispecific antibodies with cytokine-stimulated effector cells for immunotherapy of renal cell carcinoma.

BACKGROUND: Bispecific antibodies--consisting of a F(ab')-fragment derived from a monoclonal antibody against a tumor epitope as well as of another antibody against a cytotoxic trigger molecule on immune effector cells--can improve the effectiveness of antibody-based tumor therapy. MATERIALS AND METHODS: We used bispecific antibodies with one specifity against the EGF-receptor, which is overexpressed on the majority of renal cell carcinomas, and another specifity against Fc receptors on human leukocytes (Fc gamma RI/CD64; Fc gamma RIII/CD16 and Fc alpha RI/CD89). As source of effector cells, whole blood from patients treated with G-CSF, GM-CSF or IL2/IFN-alpha was used in 51Cr- release assays using various renal cancer cell lines as tumor targets. Further experiments with Percoll-isolated granulocytes or mononuclear cells from the same donors were performed in order to identify the active effector cell populations. RESULTS: Compared with conventional monoclonal EGF-R directed antibodies (murine IgG2a, humanized IgG1), bispecific antibodies induced significantly enhanced cytotoxicity. Highest amounts of tumor cell killing were observed using whole blood from patients treated with G-CSF or GM-CSF in combination with an [Fc alpha RI x EGF-R] bispecific antibody. Under these conditions, granulocytes constituted the most active effector cell population. CONCLUSION: The combination of myeloid growth factors and bispecific antibodies offer a promising new approach for the treatment of advanced renal cell carcinoma.

Animals↗

Predominance of T-lymphocytes with a high-affinity receptor for sheep red blood cells in the synovial fluid of patients with rheumatoid arthritis. A short communication.

Using different modifications of the spontaneous rosette-forming assay, T-lymphocytes were determined in the synovial fluid and the peripheral blood of patients with rheumatoid arthritis (RA). It was shown that a T-lymphocyte subpopulation, forming E-rosettes by a high affinity receptor for SRBC was enriched in the synovial fluid as compared to the peripheral blood.

Animals↗